Distribution and antitumor activity of adriamycin given in a high-dose and a repeated low-dose schedule to mice

Experimental studies on the distribution of adriamycin (AM) under different treatment conditions and possible correlations between tissue and plasma levels and chemotherapeutic activity are discussed. C57BL/6J mice bearing im Lewis lung carcinoma and (C3H x O2O)F1 mice bearing mammary carcinoma were injected iv with AM at a single dose of 15 mg/kg or with the same total amount of drug administered in spaced doses of 3.75 mg/kg for 4 consecutive days. In the two experimental systems studied, the drug reached approximately the same value in the tumor and spleen with both types of treatment, but with the 3.75-mg/kg x 4 schedule much lower AM concentrations were observed in the heart than with the single high-dose treatment. The therapeutic activity of the two treatments also differed: the antitumor and antimetastatic effect was the same in the two tumor systems, but with the 3.75-mg/kg x 4 schedule, increased survival and somewhat lower toxicity were observed. Daunorubicin, tested in the mammary carcinoma system with the two schedules of treatment, behaves very similarly to AM in terms of both distribution and chemotherapeutic effect.